Olefin metathesis in the synthesis of benzopyran, benzofuran and flavonoid scaffolds

Though well-established in the petrochemical industry, olefin metathesis is gaining interest in the pharmaceutical, fine chemical and natural product sectors. This review will focus on the application of metathesis, and predominantly ring-closing metathesis, in the synthesis of benzopyrans and benzofurans, with special sections devoted to 2-aryl- and 3-arylbenzo[b]furans and flavonoids. The metathesis catalysts applied for this purpose are dominated by the robust and commercially available Grubbs first and second-generation catalysts, with typical catalyst loads of 5–10 mol%. The preparation of the diene substrates typically involved O-allylation, thermal or microwave driven Claisen rearrangements, isomerisation of allylic double bonds, O-vinylation and methylenation of carbonyl groups. The preparation of arylbenzofurans and flavonoids in addition involved Friedel-Crafts acylation, benzoylation, O-alkylation of 2-haloacetophenones, Sakurai-Hosomi type condensation of allyl oxasilanes or allyl boranes with benzaldehydes, Heck-Matsuda arylation, a Grignard reaction (with ArMgBr) followed by oxidation and Wittig methylenation or a Grignard reaction – β-elimination sequence.